Postprandial gallbladder emptying in patients with type 2 diabetes: potential implications for bile-induced secretion of glucagon-like peptide 1

Abstract

Objective: Recent preclinical work has suggested that postprandial flow of bile acids into the small intestine potentiates nutrient-induced glucagon-like peptide 1 (GLP1) secretion via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells. The notion of bile-induced GLP1 secretion combined with the findings of reduced postprandial gallbladder emptying in patients with type 2 diabetes (T2DM) led us to speculate whether reduced postprandial GLP1 responses in some patients with T2DM arise as a consequence of diabetic gallbladder dysmotility. Design and methods: In a randomised design, 15 patients with long-standing T2DM and 15 healthy age-, gender-and BMI-matched control subjects were studied during 75-g oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolaemic (350 ml) liquid meals: i) 2.5 g fat, 107 g carbohydrate and 13 g protein; ii) 10 g fat, 93 g carbohydrate and 11 g protein; and iii) 40 g fat, 32 g carbohydrate and 3 g protein. Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP1, glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin and gastrin were measured. Furthermore, gallbladder emptying and gastric emptying were examined. Results: Gallbladder emptying increased with increasing meal fat content, but no intergroup differences were demonstrated. GIP and GLP1 responses were comparable among the groups with GIP levels being higher following high-fat meals, whereas GLP1 secretion was similar after both OGTT and meals. Conclusions: In conclusion, patients with T2DM exhibited normal gallbladder emptying to meals with a wide range of fat content. Incretin responses were similar to that in controls, and an association with postprandial gallbladder contraction could not be demonstrated.

Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

“…Interestingly, even oral glucose resulted in increased TBA plasma concentrations in T2D patients, whereas concentrations in NGT subjects were almost unaffected. This could fit with our finding of increased gallbladder emptying in the T2D group (ϳ30% vs. ϳ20% in NGT group) following the OGTT (11). Indeed, oral glucose is a minor stimulus for gallbladder contraction but -perhaps counterintuitivelya rather good stimulus for FGF-19 secretion as recently demonstrated by Morton et al (29).…”

“…Written informed consent was obtained from all participants. Results on postprandial glucose metabolism, gallbladder emptying and gut hormone secretion have been reported previously (11).…”

“…Hence, postprandial concentrations of bile acids were clearly influenced acutely by meal composition. Most likely, this reflected increased gallbladder emptying following a larger fat stimulus (11) and increased enterohepatic circulation of all bile acid species, but it could also point towards the notion of acute effects of macronutrient composition constituting an important regulator of postprandial bile acid pool composition similar to changes seen after more extensive diet changes (28). Indeed, the meals differed also with regard to carbohydrate and protein content.…”

“…Detailed description of the experimental procedures and subjects was provided previously (11). In short, plasma was obtained from 15 patients with T2D (mean duration of T2D: 7.5 years (range 6 -20); age: 59.4 Ϯ 9.6 years (mean Ϯ SD); BMI: 28.0 Ϯ 2.2 kg/m 2 ; hemoglobin A 1c (HbA 1c ): 7.5 Ϯ 1.4%) and 15 healthy age, gender and BMI-matched control subjects (age: 59.7 Ϯ 10.0 years; BMI: 27.9 Ϯ 2.0 kg/m 2 ; HbA 1c : 5.2 Ϯ 0.2%).…”

Pancreatic Amylase and Lipase Plasma Concentrations Are Unaffected by Increments in Endogenous GLP-1 Levels Following Liquid Meal Tests

“…Detailed description of the experimental procedures and subjects was provided previously (4). In short, pancreas-specific amylase and lipase concentrations were measured in plasma from 15 patients with type 2 diabetes (mean duration of diabetes: 7.5 years [range 6-20]; age: 59.4 6 9.6 years [mean 6 SD]; BMI: 28.0 6 2.2 kg/m 2 ; HbA 1c : 7.5 6 1.4% [58.0 6 15.4 mmol/mol]) and 15 healthy age-, sex-, and BMI-matched control subjects (age: 59.7 6 10.0 years; BMI: 27.9 6 2.0 kg/m 2 ; HbA 1c : 5.2 6 0.2% [33.0 6 2.2 mmol/mol]) undergoing four separate "meal" tests: a 75-g oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolemic (350 mL) liquid meals (Fig.…”